Evolution of Plasmid-Mediated Antibiotic Resistance in the Clinical Context

Abstract

Antibiotic-resistant infections are an urgent problem in clinical settings because they sharply increase mortality risk in critically ill patients. The horizontal spread of antibiotic resistance genes among bacteria is driven by bacterial plasmids, promoting the evolution of resistance. Crucially, particular associations exist between resistance plasmids and bacterial clones that become especially successful in clinical settings. However, the factors underlying the success of these associations remain unknown. Recent in vitro evidence reveals (i) that plasmids produce fitness costs in bacteria, and (ii) that these costs are alleviated over time through compensatory mutations. I argue that plasmid-imposed costs and subsequent compensatory adaptation may determine the success of associations between plasmids and bacteria in clinical settings, shaping the in vivo evolution of antibiotic resistance.

Cartography of opportunistic pathogens and antibiotic resistance genes in a tertiary hospital environment

“…As plasmids serve as an important medium for the evolution and spread of antibiotic resistance genes and emergence of multidrug resistant bacteria [40][41][42] , we identified sequences belonging to plasmids in our genomic database and further characterized them (Methods). In total, we recovered 696Mbp of putative plasmid sequences (5910 closed/circular sequences and 493Mbp of linear fragments), with most not present in existing databases for complete plasmids 43 (>90%, 1505/1588 plasmid clusters; Methods), highlighting the unexplored genetic diversity in the hospital environment.…”

Satellite tracking of gulls and genomic characterization of faecal bacteria reveals environmentally mediated acquisition and dispersal of antimicrobial‐resistant Escherichia coli on the Kenai Peninsula, Alaska

“…Multidrug‐resistant (MDR) Enterobacteriaceae, in particular, present substantial health and economic burdens (Alvarez‐Uria, Gandra, Mandal, & Laxminarayan, ; Stewardson et al, ). The proliferation of these bacteria, including MDR Escherichia coli , has been largely attributed to the horizontal acquisition of AMR genes (Leverstein‐van Hall et al, ; San Millan, ), a mechanism that may occur in both clinical and nonclinical settings (Dolejska & Papagiannitsis, ).…”

What viruses tell us about evolution and immunity: beyond Darwin?

“…In contrast to point mutations, small insertions, or small deletions, which have conventionally been regarded as the major driving forces of evolution, the supply of new genes by HGT can cause dramatic changes to an organism almost instantaneously. In addition to HGT, major genetic changes are induced by crossover and recombination events, (retro)transposition activity, transformation, and conjugation; well‐studied examples include uptake of plasmids that confer antibiotic resistance to a bacterial cell . Furthermore, RNA agents, including RNA viruses and viroids, typically lack proofreading mechanisms during their replication and thus can accumulate mutations more rapidly than replicating DNAs .…”

“…In addition to HGT, major genetic changes are induced by crossover and recombination events, (retro)transposition activity, transformation, and conjugation; [3][4][5][6] well-studied examples include uptake of plasmids that confer antibiotic resistance to a bacterial cell. 7 Furthermore, RNA agents, including RNA viruses and viroids, typically lack proofreading mechanisms during their replication and thus can accumulate mutations more rapidly than replicating DNAs. 8,9 Retroviruses, with their high genomic plasticity and life cycle that includes obligatory integration into the host genome, are among the major drivers of evolution by, among other things, providing novel genes and regulatory elements.…”